TY - JOUR
T1 - Molecular Mechanism of Resolving Trinucleotide Repeat Hairpin by Helicases
AU - Qiu, Yupeng
AU - Niu, Hengyao
AU - Vukovic, Lela
AU - Sung, Patrick
AU - Myong, Sua
N1 - Funding Information:
We thank the Myong Laboratory members for helpful discussions and Jordan Billingsley for editing the manuscript. Support for this work was provided by NIH Director’s New Innovator Award (343 NIH 1 DP2 GM105453 A) and American Cancer Society (Research Scholar Grant; RSG-12-066-01-DMC) for S. M. and Y. Q.
PY - 2015/6/3
Y1 - 2015/6/3
N2 - Summary Trinucleotide repeat (TNR) expansion is the root cause for many known congenital neurological and muscular disorders in human including Huntington's disease, fragile X syndrome, and Friedreich's ataxia. The stable secondary hairpin structures formed by TNR may trigger fork stalling during replication, causing DNA polymerase slippage and TNR expansion. Srs2 and Sgs1 are two helicases in yeast that resolve TNR hairpins during DNA replication and prevent genome expansion. Using single-molecule fluorescence, we investigated the unwinding mechanism by which Srs2 and Sgs1 resolves TNR hairpin and compared it with unwinding of duplex DNA. While Sgs1 unwinds both structures indiscriminately, Srs2 displays repetitive unfolding of TNR hairpin without fully unwinding it. Such activity of Srs2 shows dependence on the folding strength and the total length of TNR hairpin. Our results reveal a disparate molecular mechanism of Srs2 and Sgs1 that may contribute differently to efficient resolving of the TNR hairpin.
AB - Summary Trinucleotide repeat (TNR) expansion is the root cause for many known congenital neurological and muscular disorders in human including Huntington's disease, fragile X syndrome, and Friedreich's ataxia. The stable secondary hairpin structures formed by TNR may trigger fork stalling during replication, causing DNA polymerase slippage and TNR expansion. Srs2 and Sgs1 are two helicases in yeast that resolve TNR hairpins during DNA replication and prevent genome expansion. Using single-molecule fluorescence, we investigated the unwinding mechanism by which Srs2 and Sgs1 resolves TNR hairpin and compared it with unwinding of duplex DNA. While Sgs1 unwinds both structures indiscriminately, Srs2 displays repetitive unfolding of TNR hairpin without fully unwinding it. Such activity of Srs2 shows dependence on the folding strength and the total length of TNR hairpin. Our results reveal a disparate molecular mechanism of Srs2 and Sgs1 that may contribute differently to efficient resolving of the TNR hairpin.
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U2 - 10.1016/j.str.2015.04.006
DO - 10.1016/j.str.2015.04.006
M3 - Article
C2 - 26004439
AN - SCOPUS:84930384187
VL - 23
SP - 1018
EP - 1027
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 6
M1 - 3163
ER -